News Release

Oral ENT-01 safe, significantly improves constipation in persons with Parkinson disease

Embargoed news from Annals of Internal Medicine

Peer-Reviewed Publication

American College of Physicians

1. Oral ENT-01 safe, significantly improves constipation in persons with Parkinson disease
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A randomized controlled trial of 150 persons with Parkinson disease has found that (oral squalamine phosphate) ENT-01 is safe for up to 25 days of treatment and significantly improves constipation and possibly neurological symptoms. The findings are published in Annals of Internal Medicine.

Parkinson disease is a progressive neurodegenerative disorder caused by accumulation of a-synuclein (aS) in the enteric (ENS) and central nervous system (CNS). In addition to motor symptoms, persons with Parkinson disease may experience constipation, disturbances in sleep architecture, cognitive dysfunction, psychosis, and depression, all of which result from impaired function of neural pathways not restored by replacement of dopamine. Previous research has demonstrated that ENT-01 rapidly and safely improves bowel function, and also improves neuropsychiatric symptoms such as dementia and psychosis.

Researchers from the Mayo Clinic and other centers conducted a randomized controlled trial of 150 persons with Parkinson disease and constipation who were given either ENT-01 or a placebo daily for up to 25 days. The authors found that orally administered ENT-01 is safe and that it rapidly normalizes bowel function in a dose-dependent fashion with an effect that seems to persist for several weeks beyond the treatment period. They note that this suggests that the ENS is not irreversibly damaged in PD, even though the long-term constipation might suggest otherwise. They also report that adverse events, including nausea and diarrhea, were largely confined to the gastrointestinal tract, supporting the local action of ENT-01. The authors advise that in future studies, starting at lower doses and escalating more slowly may reduce the frequency of both symptoms. They also advise that, given the brief treatment period, the safety of ENT-01 will need to be evaluated for longer exposures in future studies.

Media contacts: For an embargoed PDF, please contact Angela Collom at To speak with the corresponding author, Denise Barbut, MD, please email
2. S-ICD associated with 92 percent reduction in lead-related complications typical in patients with ICDs
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The randomized multicenter ATLAS trial of more than 500 persons has found that subcutaneous implantable cardioverter defibrillators (S-ICDs) reduce perioperative, lead-related complications without significantly compromising the effectiveness of ICD shocks, but with more early postoperative pain and a trend for more inappropriate shocks. The study is published in Annals of Internal Medicine.

ICDs improve survival in patients at risk for cardiac arrest but are associated with intravascular lead-related complications. The S-ICD, with no intravascular components, was developed to minimize lead-related complications.

Researchers from McMaster University conducted a randomized multicenter trial of 544 persons with a primary or secondary prevention indication for an ICD. The authors found that S-ICD usage demonstrated a 92 percent reduction of lead-related complications and prevented most lead-related perioperative complications, including myocardial perforation, which can lead to death. They also reported a modest reduction in system reliability with the S-ICD, specifically a trend toward more inappropriate shocks. After a mean follow-up of 2.5 years, there was a nonsignificant 22 percent reduction in the need for surgical ICD revision with the S-ICD and ongoing, longer-term follow-up of ATLAS participants will evaluate the effect that the S-ICD will have on chronic ICD performance and the need for ICD reoperation.

Media contacts: For an embargoed PDF, please contact Angela Collom at To speak with the corresponding author, Jeff S. Healey, MD, MSc, please email
3. 3-step framework helps health care systems identify high-need, high-cost patients
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Researchers from the RTI-University of North Carolina (UNC) Evidence-based Practice Center, Research Triangle Park, NC developed a 3-step process to help health care systems identify high-need, high-cost (HNHC) patients. Identifying these patients at early stages can help control hospital and clinic costs. The full review and framework are published in Annals of Internal Medicine.

Finding ways to improve outcomes and reduce spending for patients with complex and costly care needs requires an understanding of their unique needs and characteristics. HNHC patients are those who have multiple chronic conditions or functional limitations, and their care can be further complicated by behavioral health conditions and social risk factors. A challenge for clinicians, health systems, and payers is to distinguish HNHC patients from the larger population of patients with chronic conditions.

Starting from a National Academy of Medicine (NAM) taxonomy, researchers used a “best fit” framework synthesis approach to examine characteristics and criteria to identify HNHC adult patients, defined as those with high use (emergency department, inpatient, or total services) or high cost. Based on their review of 64 studies published in 65 articles, the researchers created a 3-step process for identifying such patients in the health care setting: 1) identify clinical or functional risks; 2) assess for behavior or social risk factors; and 3) identify patterns of health care usage. Patients with multiple comorbidities or chronic clinical conditions, such as heart disease, chronic kidney disease, diabetes, chronic lung disease, cancer, hypertension, and chronic pain were more likely to be HNHC users. Also, having mental illness or substance use disorders or facing poverty, homelessness, or food insecurity increased the risk of being HNHC health care users. Finally, those with a pattern of high health care use in the past were more likely to continue this pattern. According to the researchers, this framework could be a good place to start to help improve quality and efficiency of care in hospitals and clinics.

The authors of an accompanying editorial from the University of Pittsburgh Graduate School of Public Health offer a real-world perspective on how the modified framework contributes to identifying patient needs, what appears to be missing, and possible next steps. They note that more data on patient demographics and characteristics may help to improve the taxonomy, as could incorporating ways to identify mismatched care.

Media contacts: For an embargoed PDF, please contact Angela Collom at To speak with the corresponding author, please contact, Eva Chang, PhD at
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